Method for green and convenient synthesis of diaryl selenium sulfoxide without catalyst

Abstract

The invention relates to a method for directly synthesizing diaryl selenium sulfoxide from aryl seleninic acid. According to the method, aryl seleninic acid and a (hetero) arene compound are taken as substrates, and a series of different diaryl selenium sulfoxide compounds are directly prepared through reaction. The process conditions are reasonable, and the operation is simple and safe; the method has the advantages of simple operation, no need of any catalyst, simple post-treatment, environmental protection, and provision of a green and efficient approach for the preparation of diaryl selenium sulfoxide in a highly concise manner, and avoids the use of additives such as an oxidizing agent and alkali in the conventional synthesis method.

Description

Technical Field

[0001] This invention relates to the fields of organic synthesis, pharmaceutical synthesis, and organic chemical engineering, and to a method for directly synthesizing diarylselenide sulfoxide from (hetero)aromatic hydrocarbons and aryl selenite. Background Technology

[0002] Indole, aromatic amines, thiophene, and other heteroaromatic compounds are not only important pharmacophores, but also widely present in functional molecules such as materials and fluorescent probes. Selenium is an essential trace element for the human body and is one of the active sites of many enzymes. Many selenium compounds have been shown to have significant pharmacological activities. Diaryl selenium sulfoxides can be used as oxidants, organic synthesis intermediates, and pharmacophores, and have also been shown to have inhibitory activity against tumor cell proliferation (Z.Wen, J.Xu, Z.Wang, H.Qi, Q.Xu, Z.Bai, Q.Zhang, K.Bao, Y.Wu, W.Zhang, Eur.J.Med.Chem.2015, 90, 184-194; Shenyang Pharmaceutical University. Substituted phenylindole selenide, selenium sulfoxide, selenium sulfone and their use as tumor cell proliferation inhibitors: CN201310598262.8[P].2014-03-19.).

[0003] The reported methods for preparing diaryl selenide sulfoxides mainly include: first synthesizing diaryl selenide via a transition metal-mediated reaction (L. Wang, M. Wang, F. Huang, Synlett 2005, 2005, 2007-2010.) or an oxidant (Y. Wang, Y. Zhang, C. Zhou, Y. Jiang, Y. Xu, X. Zeng, G. Liu, Org. Biomol. Chem. 2022, 20, 5463-5469.), followed by oxidation with an oxidant to obtain the target product (Jiyang College, Zhejiang A&F University. A method for preparing phenyl-N-methylpyrrole selenide sulfoxides by copper catalysis: CN2020). 10736082.1[P].2020-12-11; Z.Wen, J.Xu, Z.Wang, H.Qi, Q.Xu, Z.Bai, Q.Zhang, K.Bao, Y.Wu, W.Zhang, Eur.J.Med.Chem.2015,90,184-194; Shenyang Pharmaceutical University. Substituted phenylindolyl selenide, selenium sulfoxide, selenium sulfone and their use as tumor cell proliferation inhibitors: CN201310598262.8[P].2014-03-19.). However, the above methods inevitably have some shortcomings, such as: redundant reaction steps, high reaction temperature, poor functional group compatibility, limited substrate applicability, need for metal catalysts or bases and other additives, and the use of odorous selenophenols, etc. Summary of the Invention

[0004] Therefore, it is necessary to provide a green, substrate-compatible, mild, convenient, and efficient method for synthesizing diaryl selenide sulfoxides.

[0005] The purpose of this invention is to provide a green and efficient route for the preparation of diaryl selenide sulfoxide in a highly concise manner, requiring no catalyst, with simple post-processing, and being environmentally friendly.

[0006] This invention is achieved through the following technical solutions:

[0007] A convenient method for synthesizing diarylselenide sulfoxide under mild conditions without the need for a catalyst, characterized by proceeding according to the following reaction equation:

[0008]

[0009] The process includes the following steps: using the (hetero)aromatic hydrocarbon compound represented by Formula I and the selenite compound represented by Formula II as raw materials, a reaction is carried out, and after the reaction is completed, the diaryl selenite sulfoxide compound represented by Formula III is obtained by separation and purification.

[0010] The (hetero)aromatic hydrocarbon compound Ar 1 Including substituted or unsubstituted C 6-20 Aromatics, substituted or unsubstituted C 4-20 heteroaromatics;

[0011] Ar in the selenite compound 2 Including substituted or unsubstituted C 6-20 aryl, substituted or unsubstituted C 3-20 Mixed aromatics;

[0012] Compared with the prior art, the present invention has the following advantages:

[0013] (1) The background art has clearly pointed out that diaryl selenide sulfoxides can be used as oxidants, organic synthesis intermediates and pharmacophores, and have also been shown to have inhibitory activity against tumor cell proliferation. Compared with the existing methods described in the background art, the present invention directly synthesizes diaryl selenide ethers in one step under mild conditions, which is simpler and faster; no heating or additional equipment such as low-temperature reactors are required, and the target product can be synthesized efficiently at room temperature, thus having advantages such as higher safety factor and large-scale industrial production application.

[0014] (2) The only byproduct of the method of the present invention is water, and the reaction solvent can be recycled and reused. It does not produce waste gas, waste liquid and waste residue, which is in line with the green chemistry concept advocated at present.

[0015] (3) Existing technologies use raw materials with unpleasant odors such as selenol or unstable properties such as diselenide. The selenite raw material used in this invention is easy to prepare, has a wide variety, and is chemically stable. It can be stored for a long time and is solid, which facilitates transportation. This provides an important foundation for large-scale promotion and application in the future.

[0016] (4) The reaction conditions of this invention are mild and do not require the use of any catalysts, metals, bases or oxidants. Therefore, it is compatible with various functional groups and provides a reliable strategy for the convenient synthesis of functional molecules such as drugs and materials.

[0017] Furthermore, Ar 1 Including substituted or unsubstituted indoles, benzene, thiophene; Ar 2 This includes substituted or unsubstituted aryl groups. Its advantage lies in the fact that indole, benzene, thiophene, and other compounds are essential structural units in functional molecules such as drugs and materials.

[0018] Furthermore, the indole includes indoles substituted with one or more of alkyl, alkynyl, (hetero)aryl, alkylaryl, alkenyl, haloyl, heteroalkyl, nitro, cyano, fluoroalkyl, carboxyl, ester, acyloxy, or acyl groups; the benzene includes benzene substituted with one or more heteroalkyl groups; the thiophene includes thiophene substituted with one or more heteroalkyl groups; and the aryl group includes aryl groups substituted with one or more of alkyl, alkoxy, or haloyl groups. Its advantage lies in that the functional groups can be further modified to obtain complex functional molecules, which facilitates the convenient establishment of functional molecule libraries.

[0019] Further, the indole includes 1-methylindole, 1,4-dimethylindole, 1-methyl-4-fluoroindole, 1-methyl-4-bromoindole, 1,5-dimethylindole, 1-methyl-5-methoxyindole, 1-methyl-5-fluoroindole, 1-methyl-5-chloroindole, 1-methyl-5-bromoindole, 1-methyl-5-iodoindole, 1-methyl-5-nitroindole, 1,2-dimethylindole, 1,2-dimethyl-5-methoxyindole, 1-methyl-6-fluoroindole, 1-methylindole-6-carboxaldehyde, methyl 1-methylindole-6-carboxylate, 1-methyl-6-cyanoindole, 1-methyl-6-nitroindole, 1-methyl-6-trifluoromethylindole, 1,7-dimethylindole, 1-methyl-7-methoxyindole, 1-isopropylindole, 1-allylindole, 1 -Benzylindole, 1-(2-pentynyl)indole, 1-phenylindole, 2-methyl-1-ethylindole, 1-ethyl-2-phenylindole, 1-benzylindole-6-carboxylic acid, 1-methyl-2-phenyl-5-methoxyindole, 1,2-dimethyl-5-chloroindole, (S)-2-(4-isobutylphenyl)propionic acid-1-methyl-5-indole methyl ester; the benzene includes 1,3,5-trimethoxybenzene and N-methylaniline; the thiophene includes 2-methoxythiophene, 3-methoxythiophene, and 3,4-ethylenedioxythiophene; the aryl group includes 2-methylphenyl, 4-methylphenyl, 4-ethylphenyl, 4-methoxyphenyl, 3,4,5-trimethoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 2-bromophenyl, 3,4,5-trimethoxyphenyl, and 2-naphthyl. Its advantage lies in the fact that the above structures are important structural units in functional molecules such as drugs and materials. For example, (S)-2-(4-isobutylphenyl)propionic acid-1-methyl-5-indole methyl ester is a derivative of the drug ibuprofen; 1-methyl-2-phenyl-5-methoxyindole is ACT11778, a bactericide.

[0020] Furthermore, the reaction is carried out in a solvent, which includes any one or a mixture of several of the following: water, N,N-dimethylformamide, dimethyl sulfoxide, ethanol, 2,2,2-trifluoroethanol, 1,1,1,3,3,3-hexafluoro-2-propanol, methanol, isopropanol, tert-butanol, polyethylene glycol, ether solvents, and halogenated hydrocarbons. Preferably, the solvents are ethanol, 2,2,2-trifluoroethanol, 1,1,1,3,3,3-hexafluoro-2-propanol, methanol, and isopropanol, with 2,2,2-trifluoroethanol being the most preferred. The advantage is that the preferred solvents have low toxicity and are low-boiling-point solvents, facilitating recovery and reuse.

[0021] Furthermore, the molar ratio of the (hetero)aromatic compound represented by Formula I to the selenite compound represented by Formula II is 1–10:1–10, preferably 2–5:2–5, and most preferably 2:1. The advantage is that the more readily available raw material is used, which helps reduce costs and facilitates further promotion and application.

[0022] Furthermore, the reaction is characterized by a reaction temperature of -10 to 120°C, preferably 20 to 80°C, and most preferably 25°C; and a reaction time of 2 to 48 hours, preferably 6 to 24 hours, and most preferably 12 hours. Its advantages are that the optimal temperature is easily achieved, requiring no additional equipment such as heating or a low-temperature reactor, resulting in a higher safety factor and facilitating further application and promotion. The moderate reaction time is beneficial for improving production efficiency.

[0023] Furthermore, the method can be carried out in an inert atmosphere, an oxygen atmosphere, or an air atmosphere, but is preferably carried out in an air atmosphere. Its advantage is that the preferred atmosphere is air, eliminating the need for gas cylinders and thus improving production safety.

[0024] Further, the separation and purification includes the following operations: after the reaction is completed, the reaction solvent is directly concentrated to obtain a residue, and the residue is separated by silica gel column chromatography to obtain the diaryl selenide sulfoxide compound represented by Formula III.

[0025] Furthermore, the separation and purification process includes the following steps: after the reaction is completed, the reaction solvent is directly concentrated to obtain a residue, which is then recrystallized to obtain the diaryl selenide sulfoxide compound represented by Formula III. The advantage is that the separation and purification process is simple and easy to implement, which is beneficial for large-scale production. Detailed Implementation

[0026] The present invention will be further described in detail below with reference to specific embodiments. The present invention can be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided to provide a thorough and complete understanding of the disclosure of the present invention.

[0027] The synthetic steps of this invention involve adding 0.5 mmol of a heteroaryl hydrocarbon, 1 mL of 2,2,2-trifluoroethanol, and 0.25 mol of aryl selenite to a dried 25 mL ground glass tube equipped with a magnetic stirrer. The tube is then stoppered and reacted at room temperature for 12 hours. The reaction is confirmed to be complete by TLC. The reaction solvent is then removed by vacuum distillation, and the residue is separated by silica gel column chromatography (using a mixture of dichloromethane and methanol as eluent, with a volume ratio of 10:1) to obtain diaryl selenite sulfoxide in yields of 45-98%. Specific examples and characterization results are as follows. The structures of all products were determined by comparison of NMR and mass spectrometry results.

[0028]

[0029] Example 1: Preparation of Product 3

[0030] 1-Methylindole (0.5 mmol), 2,2,2-trifluoroethanol (1 mL), and benzeneselenic acid (0.25 mol) were added to a dried 25 mL ground glass joint test tube equipped with a magnetic stirrer. The tube was then stoppered and reacted at room temperature for 12 hours. The reaction was confirmed to be complete by TLC. The reaction solvent was then removed by vacuum distillation. The residue was separated by silica gel column chromatography (eluent was a mixture of dichloromethane and methanol, volume ratio 10:1) or recrystallized to give a white solid 3 in 92% yield.

[0031] 1-methyl-3-(phenylseleninyl)-1H-indole(3) 1 H NMR(400MHz, CDCl3)δ7.75–7.63(m,2H),7.45–7.32(m,4H),7.30(s,1H),7.2 0(d,J=8.3Hz,1H),7.14(t,J=7.7Hz,1H),7.00(t,J=7.6Hz,1H),3.61(s,3H). 13 C NMR(100MHz, CDCl3)δ141.0,137.5,132.3,130.8,129.4,126.6,125.8,123.1,121.2,119.4,112.5,110.1,33.32.HRMS(ESI)calcdfor C 15 H 14 NOSe + m / z[M+H] + :304.0241; found:304.0244.

[0032] Example 2: Preparation of Product 4

[0033] Replacing 1-methylindole in Example 1 with 1,4-dimethylindole yielded a white solid 4 in 88% yield.

[0034] 1,4-dimethyl-3-(phenylseleninyl)-1H-indole(4) 1 H NMR (400MHz, CDCl3) δ7.75–7.70(m,2H),7.46–7.42(m,3H),7.29(s,1H),7.16(d,J=4.1Hz,2H),6.97–6.92(m,1H),3.71(s,3H),2.62(s,3H). 13 C NMR(100MHz, CDCl3)δ142.9,137.7,132.0,131.0,129.9,129.5,127.0,125.9,123.2,122.4,113.9,108.0,33.5,21.4.HRMS(ESI)calcd forC 16 H 16 NOSe + m / z[M+H] + 318.0397; found: 318.0405.

[0035] Example 3: Preparation of Product 5

[0036] Replacing 1-methylindole in Example 1 with 1-methyl-4-fluoro-indole yielded white solid 5 in 87% yield.

[0037] 4-fluoro-1-methyl-3-(phenylseleninyl)-1H-indole(5) 1 H NMR (600MHz, CDCl3) δ7.79 (dd, J=7.8, 1.8Hz, 2H), 7.45–7.38 (m, 3H), 7.36 (s, 1H),7.18–7.11(m,1H),7.07(d,J=8.3Hz,1H),6.85–6.79(m,1H),3.72(s,3H). 13 C NMR (150MHz, CDCl3) δ155.7 (d, J = 247.3Hz), 143.2, 140.2 (d, J = 11.4Hz), 131.0, 130.9, 129.4, 126. 3,123.5(d,J=7.5Hz),115.1(d,J=22.0Hz),111.8,106.5(d,J=3.5Hz),106.1(d,J=18.2Hz).33.8. 19F NMR(565MHz,CDCl3)δ-118.6.HRMS(ESI)calcd for C 15 H 13 NOFSe + m / z[M+H] + :322.0146; found:322.0149.

[0038] Example 4: Preparation of Product 6

[0039] Replacing 1-methylindole in Example 1 with 1-methyl-4-bromo-indole yielded white solid 6 in 81% yield.

[0040] 4-bromo-1-methyl-3-(phenylseleninyl)-1H-indole(6) 1 H NMR (400MHz, CDCl3) δ7.76(dd,J=6.8,3.4Hz,2H),7.60(s,1H),7.37(t,J=2.8Hz,3H),7.30–7.22(m,2H),7.07(t,J=8.0Hz,1H),3.72(s,3H). 13 C NMR(100MHz, CDCl3)δ144.3,138.6,132.4,130.9,129.4,127.0,126.3,124.3,123.7,114.2,113.0,109.6,33.8.HRMS(ESI)calcd for C 15 H 12 BrNOSe + m / z[M+H] + :381.9346; found:381.9349.

[0041] Example 5: Preparation of Product 7

[0042] Replacing 1-methylindole in Example 1 with 1,5-dimethylindole yielded white solid 7 in 89% yield.

[0043] 1,5-dimethyl-3-(phenylseleninyl)-1H-indole(7) 1 H NMR (400MHz, CDCl3) δ7.78 (dd, J=5.7, 3.6Hz, 2H), 7.50–7.42 (m, 3H), 7.32–7. 23(m,2H),7.19(d,J=8.4Hz,1H),7.09–7.02(m,1H),3.72(s,3H),2.32(s,3H). 13C NMR(100MHz, CDCl3)δ141.2,135.9,132.1,130.8,130.8,129.4,126.7,126.2,125.8,124.8,119.0,109.8,33.4,21.3.HRMS(ESI)calcd for C 16 H 16 NOSe + m / z[M+H] + :318.0397; found:318.0393.

[0044] Example 6: Preparation of Product 8

[0045] Replacing 1-methylindole in Example 1 with 1-methyl-5-methoxyindole yielded a white solid 8 in 80% yield.

[0046] 5-methoxy-1-methyl-3-(phenylseleninyl)-1H-indole(8) 1 H NMR(400MHz, CDCl3)δ7.79(d,J=8.0Hz,2H),7.48–7.42(m,3H),7.29(s,1H),7.15 (d,J=9.0Hz,1H),6.83(d,J=10.6Hz,1H),6.78(s,1H),3.68(s,3H),3.61(s,3H). 13 C NMR(100MHz, CDCl3)δ155.1,140.7,132.6,132.6,130.8,129.3,126.7,126.5,113.8,112.0,110.9,100.6,55.5,33.5.HRMS(ESI)calcd for C 16 H 16 NO2Se + m / z[M+H] + :334.0346; found:334.0343.

[0047] Example 7: Preparation of Product 9

[0048] Replacing 1-methylindole in Example 1 with 1-methyl-5-fluoroindole yielded white solid 9 in 86% yield.

[0049] 5-fluoro-1-methyl-3-(phenylseleninyl)-1H-indole(9) 1H NMR (400MHz, CDCl3) δ7.75–7.71(m,2H),7.49–7.35(m,4H),7.18–7.13(m,1H),7.05(d,J=8.8Hz,1H),6.92–6.88(m,1H),3.68(s,1H). 13 C NMR (100MHz, CDCl3) δ158.4(d,J=237.7Hz),140.8,134.2,133.6,131.0,129.4,126.5,126.2(d,J= 10.8Hz), 112.5 (d, J = 5.5Hz), 111.7 (d, J = 26.5Hz), 111.1 (d, J = 9.9Hz), 104.8 (d, J = 25.1Hz), 33.6. 19 F NMR(376MHz,CDCl3)δ-121.6.HRMS(ESI)calcd for C 15 H 13 NOSeF + m / z[M+H] + :322.0146; found:322.0153.

[0050] Example 8: Preparation of Product 10

[0051] Replacing 1-methylindole in Example 1 with 1-methyl-5-chloroindole yielded a white solid 10 in 90% yield.

[0052] 6-chloro-1-methyl-3-(phenylseleninyl)-1H-indole(10) 1 H NMR (400MHz, CDCl3) δ7.47(d,J=5.0Hz,2H),7.20–7.13(m,4H),7.08(s,1H),6.87(q,J=8.8Hz,2H),3.42(s,3H). 13 C NMR(100MHz, CDCl3)δ140.8,136.0,133.2,131.1,129.5,127.1,126.8,126.5,123.6,118.9,112.4,111.2,33.5.HRMS(ESI)calcd for C 15 H 13 NOClSe + m / z[M+H] + :337.9851; found:337.9857.

[0053] Example 9: Preparation of Product 11

[0054] Replacing 1-methylindole in Example 1 with 1-methyl-5-bromoindole yielded a white solid 11 in 88% yield.

[0055] 5-bromo-1-methyl-3-(phenylseleninyl)-1H-indole(11) 1 H NMR (400MHz, CDCl3) δ7.74(d,J=9.3Hz,2H),7.58(s,1H),7.45(d,J=5.4Hz,3H),7.33(s,1H),7.25(d,J=9.0Hz,1H),7.12(d,J=8.8Hz,1H),3.70(s,3H). 13 C NMR(100MHz, CDCl3)δ140.7,136.2,133.1,131.1,129.5,127.4,126.5,126.2,122.0,114.7,112.3,111.7,33.5.HRMS(ESI)calcd for C 15 H 13 NOSeBr + m / z[M+H] + :381.9346; found:381.9341.

[0056] Example 10: Preparation of Product 12

[0057] Replacing 1-methylindole in Example 1 with 1-methyl-5-iodoindole yielded white solid 12 in 94% yield.

[0058] 6-iodo-1-methyl-3-(phenylseleninyl)-1H-indole(12) 1 H NMR (400MHz, CDCl3) δ7.54(s,1H),7.52–7.47(m,2H),7.23–7.16(m,3H),7.03(s,1H),6.99(s,1H),6.79(d,J=8.7Hz,1H),3.46(s,3H). 13 C NMR(100MHz, CDCl3)δ140.9,136.2,132.7,131.7,131.2,129.6,128.3,126.6,112.1,83.9,33.6.HRMS(ESI)calcd for C 15 H 12 NOSeINa + m / z[M+Na] +:451.9026; found:451.9031.

[0059] Example 11: Preparation of Product 13

[0060] 1-Methyl-5-nitroindole was used instead of 1-methylindole in Example 1, the reaction temperature was changed to 50°C, and the reaction time was changed to 24 hours, to obtain white solid 13 with a yield of 45%.

[0061] 1-methyl-5-nitro-3-(phenylseleninyl)-1H-indole(13) 1 H NMR (400MHz, CDCl3) δ8.30(s,1H),7.96(d,J=8.9Hz,1H),7.80–7.76(m,2H),7.68(s,1H),7.56(d,J=8.9Hz,1H),7.53–7.48(m,3H),3.91(s,3H). 13 C NMR(100MHz, CDCl3)δ143.4,140.9,137.0,136.5,131.5,130.6,129.8,126.6,119.9,117.9,113.7,107.2,34.0.HRMS(ESI)calcd forC 15 H 12 NOSeINa + m / z[M+H] + :349.0086; found:349.0081.

[0062] Example 12: Preparation of Product 14

[0063] Replacing 1-methylindole in Example 1 with 1,2-dimethylindole yielded white solid 14 in 94% yield.

[0064] 1,2-dimethyl-3-(phenylseleninyl)-1H-indole(14) 1 H NMR (400MHz, CDCl3) δ7.77–7.71(m,2H),7.43(d,J=6.8Hz,3H),7.31(d,J=8.0Hz,1H),7.24(d,J=8. 5Hz,1H),7.14(t,J=7.7Hz,1H),6.97(t,J=7.5Hz,1H),3.63(d,J=2.2Hz,3H),2.58(d,J=2.3Hz,3H). 13C NMR(100MHz, CDCl3)δ141.7,140.9,137.2,130.4,129.3,126.7,125.7,122.3,121.2,119.0,109.4,29.8,11.6.HRMS(ESI)calcd for C 16 H 16 NOSe + m / z[M+H] + 318.0397; found: 318.0400.

[0065] Example 13: Preparation of Product 15

[0066] Replacing 1-methylindole in Example 1 with 1,2-dimethyl-5-methoxyindole yielded a white solid 15 in 89% yield.

[0067] 5-methoxy-1,2-dimethyl-3-(phenylseleninyl)-1H-indole(15) 1 H NMR(600MHz, CDCl3)δ7.73(d,J=7.5Hz,2H),7.42–7.31(m,3H),7.04(d,J=8.9Hz, 2H),6.69(d,J=11.3Hz,1H),6.60(s,1H),3.50(s,3H),3.49(s,3H),2.50(s,3H). 13 C NMR(150MHz, CDCl3)δ154.8,141.7,140.7,132.1,130.3,129.1,126.7,126.1,112.3,110.1,108.9,100.6,55.3,29.7,11.5.HRMS(ESI)calcd for C 17 H 18 NO2Se + m / z[M+H] + :348.0503; found:348.0508.

[0068] Example 14: Preparation of Product 16

[0069] Replacing 1-methylindole in Example 1 with 1-methyl-6-fluoroindole yielded white solid 16 in 83% yield.

[0070] 6-fluoro-1-methyl-3-(phenylseleninyl)-1H-indole(16) 1H NMR (400MHz, CDCl3) δ7.77(d,J=5.2Hz,2H),7.49–7.44(m,3H),7.36(d,J=12.8Hz,2H),6.97(d,J=9.3Hz,1H),6.82(t,J=9.1Hz,1H),3.71(s,3H). 13 C NMR (100MHz, CDCl3) δ160.2 (d, J = 241.0Hz), 137.9 (d, J = 11.9Hz), 132.7 (d, J = 3.2Hz), 131.0, 12 9.4, 126.6, 122.2, 120.6 (d, J = 10.1Hz), 113.1, 110.2 (d, J = 24.8Hz), 96.7 (d, J = 26.4Hz), 33.5. 19 F NMR(376MHz,CDCl3)δ-117.9.HRMS(ESI)calcd for C 15 H 13 NOSeF + m / z[M+H] + :322.0146; found:322.0143.

[0071] Example 15: Preparation of Product 17

[0072] Replacing 1-methylindole-6-carboxaldehyde in Example 1 yielded white solid 17 in 80% yield.

[0073] 1-methyl-3-(phenylseleninyl)-1H-indole-6-carbaldehyde(17) 1 H NMR (400MHz, CDCl3) δ9.99(s,1H),7.85(s,1H),7.80–7.74(m,2H),7.60(s,1H),7.58(s,2H),7.53–7.43(m,3H),3.84(s,3H). 13 C NMR (100MHz, CDCl3) δ191.9,140.7,137.3,135.8,131.7,131.2,130.8,129.6,126.5,122.6,119.9,113.8,112.4,33.7.HRMS(ESI)calcd forC 16 H 13 NO2NaSe + m / z[M+H] + :354.0009; found:354.0016.

[0074] Example 16: Preparation of Product 18

[0075] Methyl 1-methylindole-6-carboxylate was used instead of 1-methylindole in Example 1 to give white solid 18 in 71% yield.

[0076] methyl 1-methyl-3-(phenylseleninyl)-1H-indole-6-carboxylate(18) 1 H NMR (400MHz, CDCl3) δ8.02(s,1H),7.77–7.69(m,3H),7.51–7.40(m,5H),3.85(s,3H),3.77(s,3H); 13 C NMR(100MHz, CDCl3)δ167.3,140.9,137.0,134.8,131.0,129.5,129.4,126.5,124.8,122.1,119.1,113.5,112.5,52.1,33.6.HRMS(ESI)calcd for C 17 H 16 NO3Se + m / z[M+H] + :362.0295; found:362.0291.

[0077] Example 17: Preparation of Product 19

[0078] Replacing 1-methylindole in Example 1 with 1-methyl-6-cyanoindole yielded white solid 19, with a yield of 62%.

[0079] 1-methyl-3-(phenylseleninyl)-1H-indole-6-carbonitrile(19) 1 H NMR (400MHz, CDCl3) δ7.49–7.40(m,2H),7.33(s,1H),7.29(s,1H),7.23(d,J=8.3Hz,1H),7.19–7.11(m,3H),7.00–6.91(m,1H),3.50(s,3H). 13 C NMR(100MHz, CDCl3)δ140.6,136.6,135.4,131.2,129.6,128.9,126.4,123.9,120.5,119.7,115.1,114.0,105.8,33.7.HRMS(ESI)calcd for C 16 H 13nnJC + m / z[M+H] + :329.0193; found:329.0185.

[0080] Example 18: Preparation of Product 20

[0081] 1-Methyl-6-nitroindole was used instead of 1-methylindole in Example 1, and the reaction temperature was changed to 70°C to give white solid 20, with a yield of 50%.

[0082] 1-methyl-6-nitro-3-(phenylseleninyl)-1H-indole(20) 1 H NMR (400MHz, CDCl3) δ8.30(s,1H),7.97(d,J=6.8Hz,1H),7.78(m,2H),7.68(s,1H),7.56(d,J=8.9Hz,1H),7.53–7.48(m,3H),3.91(s,3H). 13 C NMR(100MHz, CDCl3)δ144.0,140.6,137.0,136.5,131.5,130.6,129.8,126.6,119.9,116.7,114.4,107.2,34.0.HRMS(ESI)calcd forC 15 H 12 N2O3NaSe + m / z[M+H] + 370.9911; found: 370.9915.

[0083] Example 19: Preparation of Product 21

[0084] Replacing 1-methylindole in Example 1 with 1-methyl-6-trifluoromethylindole yielded white solid 21 in 92% yield.

[0085] 1-methyl-3-(phenylseleninyl)-6-(trifluoromethyl)-1H-indole(21) 1 H NMR (400MHz, CDCl3) δ7.52–7.46(m,2H),7.33–7.23(m,3H),7.20–7.15(m,3H),7.01(d,J=8.5Hz,1H),3.51(s,1H). 13C NMR (101MHz, CDCl3) δ140.8,136.6,134.5,131.2,129.6,128.2,126.5,125.3(q,J=31.9 Hz), 123.6 (q, J = 271.5Hz), 120.1, 117.9 (d, J = 3.5Hz), 113.5, 107.8 (q, J = 4.4Hz), 34.0. 19 F NMR(376MHz,CDCl3)δ-60.2.HRMS(ESI)calcd forC 16 H 12 NONaSeF3 + m / z[M+H] + 393.9934; found: 393.9941.

[0086] Example 20: Preparation of Product 22

[0087] Replacing 1-methylindole in Example 1 with 1,7-dimethylindole yielded a white solid 22 in 92% yield. 1,7-dimethyl-3-(phenylseleninyl)-1H-indole (22) 1 H NMR (600MHz, CDCl3) δ7.75(d,J=9.5Hz,2H),7.41(d,J=7.2Hz,3H),7.31(d,J=7.7Hz,1H),7.23(s,1H),6.93–6.85(m,2H),3.91(s,3H),2.62(s,3H). 13 C NMR(150MHz, CDCl3)δ141.3,136.2,133.4,130.7,129.3,127.0,126.5,125.6,122.1,121.4,117.4,112.4,37.3,19.4.HRMS(ESI)calcd forC 16 H 16 NOSe + m / z[M+H] + 318.0397; found: 318.0404.

[0088] Example 21: Preparation of Product 23

[0089] Replacing 1-methylindole in Example 1 with 1-methyl-7-methoxyindole yielded a white solid 23 in 58% yield.

[0090] 7-methoxy-1-methyl-3-(phenylseleninyl)-1H-indole(23)1 H NMR (400MHz, CDCl3) δ7.78–7.74(m,2H),7.47–7.42(m,3H),7.22(s,1H),7.04(d,J= 8.1Hz,1H),6.95(t,J=8.0Hz,1H),6.59(d,J=7.8Hz,1H),4.00(s,3H),3.85(s,3H). 13 CNMR(101MHz, CDCl3)δ148.0,141.3,132.8,130.8,129.3,128.3,127.3,126.7,122.0,112.6,111.8,103.6,55.4,37.3.HRMS(ESI)calcd for C 16 H 16 NO2Se + m / z[M+H] + :334.0346; found:334.0348.

[0091] Example 22: Preparation of Product 24

[0092] Replacing 1-methylindole in Example 1 with 1-isopropylindole yielded a white solid 24 in 66% yield. 1-isopropyl-3-(phenylseleninyl)-1H-indole (24) 1 H NMR(400MHz, CDCl3)δ7.78(d,J=4.7Hz,2H),7.60(s,1H),7.49–7.33(m,5H),7.20(t,J=7.7Hz,1H ),7.04(t,J=7.6Hz,1H),4.63(hept,J=6.7Hz,1H),1.50(d,J=6.8Hz,3H),1.48(d,J=6.8Hz,3H). 13 C NMR(100MHz, CDCl3)δ141.2,136.6,130.9,129.4,127.5,126.8,126.0,122.9,121.2,119.6,112.7,110.4,48.0,22.7,22.6.HRMS(ESI)calcd for C 17 H 18 NOSe + m / z[M+H] + :332.0554; found:332.0558.

[0093] Example 23: Preparation of Product 25

[0094] Replacing 1-methylindole in Example 1 with 1-allyl-3-(phenylseleninyl)-1H-indole (25) yielded a white solid 25 in 69% yield. 1 H NMR (400MHz, CDCl3) δ7.50(dd,J=7.4,2.3Hz,2H),7.17(d,J=5.3Hz,5H),7.02(d,J=8.3Hz,1H),6.92(t,J=7.7Hz,1H),6.7 8(t,J=7.6Hz,1H),5.63(ddt,J=15.9,10.5,5.6Hz,1H),4.93(d,J=10.2Hz,1H),4.81(d,J=17.1Hz,1H),4.43–4.37(m,2H). 13 C NMR(100MHz, CDCl3)δ141.1,137.0,132.0,131.2,130.9,129.4,126.7,126.0,123.2,121.4,119.6,118.6,113.2,110.5,49.37.HRMS(ESI)calcd for C 17 H 16 NOSe + m / z[M+H] + :330.0397; found:332.0403.

[0095] Example 24: Preparation of Product 26

[0096] Replacing 1-methylindole in Example 1 with 1-benzylindole yielded white solid 26 in 70% yield.

[0097] 1-benzyl-3-(phenylseleninyl)-1H-indole(26) 1 H NMR (600MHz, CDCl3) δ7.81 (dd, J=6.9, 2.7Hz, 2H), 7.51–7.48 (m, 2H), 7.48–7.40 (m, 3H), 7. 30–7.23(m,4H),7.20–7.14(m,1H),7.09(d,J=5.9Hz,2H),7.08–7.04(m,1H),5.24(s,2H). 13C NMR (150MHz, CDCl3) δ141.1,137.1,135.7,131.5,130.8,129.3,128.8,128.0, 126.9,126.6,126.0,123.2,121.3,119.6,113.4,110.6,50.5.HRMS(ESI)calcd for C 21 H 18 NOSe + m / z[M+H] + :380.0554; found:380.0550.

[0098] Example 25: Preparation of Product 27

[0099] Replacing 1-methylindole in Example 1 with 1-(2-pentynyl)indole or 1-phenylindole yielded a white solid 27 with a yield of 69%.

[0100] 1-(pent-2-yn-1-yl)-3-(phenylseleninyl)-1H-indole(27) 1 H NMR (400MHz, CDCl3) δ7.83–7.77(m,2H),7.60(s,1H),7.48–7.43(m,4H),7.38(d,J=8.3Hz,1H),7. 23(t,J=7.9Hz,1H),7.08(t,J=7.7Hz,1H),4.80(s,2H),2.23–2.13(m,2H),1.10(t,J=7.6Hz,3H). 13 C NMR(100MHz, CDCl3)δ141.0,136.6,130.9,130.8,129.4,126.7,126.2,123.2,121.5,119.7,113.3,110.3,88.9,71.8,36.9,13.5,12.3.HRMS(ESI)calcd for C 19 H 18 NOSe + m / z[M+H] + :356.0554; found:356.0557.

[0101] Example 26: Preparation of Product 28

[0102] Replacing 1-methylindole in Example 1 with 1-phenylindole yielded a white solid 28 in 94% yield.

[0103] 1-phenyl-3-(phenylseleninyl)-1H-indole(28) 1 H NMR (400MHz, CDCl3) δ7.86 (d, J = 5.1Hz, 2H), 7.62 (s, 1H), 7.56 (d, J = 8.0Hz, 1H), 7.44 (m, 9H), 7.21 (t, J = 7.8Hz, 1H), 7.12 (t, J = 7.6Hz, 1H). 13 C NMR(100MHz, CDCl3)δ140.8,138.2,137.1,131.0,129.8,129.5,127.8,126.7,126.3,124.7,123.9,122.0,119.7,115.7,111.3.HRMS(ESI)calcd forC 20 H 16 NOSe + m / z[M+H] + 366.0397; found: 366.0404.

[0104] Example 27: Preparation of Product 29

[0105] Replacing 1-methylindole in Example 1 with 2-methyl-1-ethylindole yielded a white solid 29, with a yield of 91%.

[0106] 1-ethyl-2-methyl-3-(phenylseleninyl)-1H-indole(29) 1 H NMR (400MHz, CDCl3) δ7.77–7.71(m,2H),7.54–7.35(m,3H),7.30(d,J=8.0Hz,1H),7.25(d,J=8.2Hz,1H) ,7.13(t,J=7.7Hz,1H),6.96(t,J=7.5Hz,1H),4.10(q,J=7.4Hz,2H),2.59(s,3H),1.32(t,J=7.1Hz,3H). 13 C NMR(100MHz, CDCl3)δ140.9,140.9,136.1,130.4,129.3,126.7,125.9,122.2,121.1,119.2,109.5,109.4,38.28,14.96,11.42.HRMS(ESI)calcd for C 17 H 18 NOSe + m / z[M+H] +:332.0554; found:332.0556.

[0107] Example 28: Preparation of Product 30

[0108] Replacing 1-methylindole in Example 1 with 1-ethyl-2-phenylindole yielded a white solid 30 in 95% yield.

[0109] 1-ethyl-2-phenyl-3-(phenylseleninyl)-1H-indole(30) 1 H NMR(400MHz, CDCl3)δ7.74(d,J=5.7Hz,2H),7.56–7.51(m,5H),7.48–7.33(m,5H),7.2 1(t,J=7.8Hz,1H),7.01(t,J=7.5Hz,1H),4.09(q,J=7.3Hz,2H),1.27(t,J=7.3Hz,3H). 13 C NMR (100MHz, CDCl3) δ144.9,140.9,136.6,130.7,130.4,129.8,129.4,129.2, 128.9,126.7,125.6,123.2,121.5,120.3,110.3,39.1,18.2.HRMS(ESI)calcd for C 22 H 20 NOSe + m / z[M+H] + :394.0712; found:394.0710.

[0110] Example 29: Preparation of Product 31

[0111] 1-Benzylindole-6-carboxylic acid was used instead of 1-methylindole in Example 1. Silica gel column chromatography (using a mixture of dichloromethane and methanol as eluent, in a volume ratio of 5:1) yielded a white solid 31 with a yield of 96%.

[0112] 1-benzyl-3-(phenylseleninyl)-1H-indole-6-carboxylic acid(31) 1 H NMR (400MHz, CDCl3) δ12.57(s,1H),8.04(s,1H),7.66(t,J=8.2Hz,3H),7.44–7.34(m,5H),7.35–7.23(m,4H),7.06(s,1H),5.28(s,2H). 13C NMR (100MHz, CDCl3) δ166.7,139.1,136.5,136.1,132.6,131.3,129.7,128.7,128 .5,128.2,128.1,126.6,124.7,122.1,118.2,115.3,111.9,66.5.HRMS(ESI)calcd for C 22 H 18 NO3Se + m / z[M+H] + :424.0452; found:424.0459.

[0113] Example 30: Preparation of Product 32

[0114] Replacing 1-methylindole in Example 1 with 2-methoxythiophene yielded a white solid 32 in 98% yield.

[0115] 2-methoxy-5-(phenylseleninyl)thiophene(32) 1 H NMR (400MHz, CDCl3) δ7.47–7.40(m,2H),7.20–7.15(m,3H),6.90(d,J=4.1Hz,1H),5.84(d,J=4.1Hz,1H),3.50(s,3H). 13 C NMR(100MHz, CDCl3)δ172.5,141.9,132.2,131.4,129.5,127.5,126.0,104.7,60.5.HR-MS(ESI)m / z calcd for C 11 H 11 O2SSe,[M+H] + :286.9645,found:286.9651.

[0116] Example 31: Preparation of Product 33

[0117] Replacing 1-methylindole in Example 1 with 3-methoxythiophene yielded a white solid 33 in 71% yield.

[0118] 3-methoxy-2-(phenylseleninyl)thiophene(33) 1 H NMR (600MHz, CDCl3) δ7.76–7.72(m,2H),7.49–7.40(m,3H),7.37(d,J=5.4Hz,1H),6.76(d,J=5.5Hz,1H),3.86(s,3H).13 C NMR(151MHz, CDCl3)δ160.6,141.7,131.4,129.5,129.1,126.4,119.2,115.2,58.6.HR-MS(ESI)m / z calcd for C 11 H 11 O2SSe,[M+H] + :286.9645,found:286.9651.

[0119] Example 32: Preparation of Product 34

[0120] Replacing 1-methylindole in Example 1 with 3,4-ethylenedioxythiophene yielded a white solid 34 in 57% yield.

[0121] 5-(phenylseleninyl)-2,3-dihydrothieno[3,4-b][1,4]dioxine(34) 1 H NMR (400MHz, CDCl3) δ7.79(dd,J=6.7,3.1Hz,2H),7.52–7.47(m,3H),6.55(s,1H),4.27(d,J=3.5Hz,2H),4.18(d,J=3.1Hz,2H). 13 C NMR(100MHz, CDCl3)δ144.8,141.2,140.5,131.5,129.4,126.4,106.8,65.2,64.3.HR-MS(ESI)m / z calcd for C 12 H 10 O3NaSSe,[M+Na] + :336.9414,found:336.9421.

[0122] Example 33: Preparation of Product 35

[0123] Replacing 1-methylindole in Example 1 with 1,3,5-trimethoxybenzene yielded a white solid 35 in 86% yield.

[0124] 1,3,5-trimethoxy-2-(phenylseleninyl)benzene(35) 1 H NMR (400MHz, CDCl3) δ7.65 (d, J = 7.0Hz, 2H), 7.42–7.30 (m, 3H), 5.99 (s, 2H), 3.75 (s, 3H), 3.60 (s, 6H). 13C NMR (100MHz, CDCl3) δ165.0,161.8,141.6,129.7,128.9,128.6,126.1,110.6,91.24,55.9,55.5.HR-MS(ESI)m / z calcd for C 15 H 17 O4Se,[M+H] + :341.0292,found:341.0291.

[0125] Example 34: Preparation of Product 36

[0126] Instead of 1-methylindole in Example 1, N-methylaniline was used, and the feed ratio of N-methylaniline and arylselenite was changed to 1:1 to obtain white solid 36 with a yield of 63%.

[0127] N-methyl-4-(phenylseleninyl)aniline(36)1H NMR (600MHz, CDCl3) δ7.50–7.45(m,2H),7.35–7.28(m,2H),7.23–7.19(m,2 H),7.18–7.13(m,1H),6.61–6.55(m,2H),4.29–3.38(brs,1H),2.86(s,3H). 13 C NMR(151MHz, CDCl3)δ149.6,137.4,134.7,129.8,129.1,125.9,114.6,113.4,30.6.HR-MS(ESI)m / z calcd for C 13 H 14 NOSe,[M+H] + :280.0235,found:280.0231.

[0128] Example 35: Preparation of Product 37

[0129] Replacing benzeneselenic acid with 4-methylbenzeneselenic acid in Example 1 yielded a white solid 37 with a yield of 65%.

[0130] 1-methyl-3-(p-tolylseleninyl)-1H-indole(37) 1H NMR (600MHz, CDCl3) δ7.58(d,J=8.4Hz,2H),7.42(d,J=8.0Hz,1H),7.24(s,1H),7.14( dd,J=8.3,5.0Hz,3H),7.12–7.07(m,1H),6.99–6.94(m,1H),3.53(s,3H),2.23(s,3H). 13 CNMR(150MHz, CDCl3)δ140.7,137.6,137.2,131.7,129.7,126.2,125.5,122.6,120.7,119.1,112.6,109.7,32.8,20.9.HR-MS(ESI)m / z calcd for C 16 H 16 NOSe,[M+H] + :318.0397,found:318.0402.

[0131] Example 36: Preparation of Product 38

[0132] Replacing benzeneselenic acid with 2-methylbenzeneselenic acid in Example 1 yielded a white solid 38 with a yield of 69%.

[0133] 1 H NMR (600MHz, CDCl3) δ8.25–8.21(m,1H),7.46–7.40(m,1H),7.40–7.32(m,1H),7.29–7.22(m,1H),7.17–6.93(m,5H),3.51(s,3H),2.14(s,3H). 13 CNMR(150MHz, CDCl3)δ138.8,136.9,136.3,131.6,130.5,130.3,126.6,125.9,125.2,122.6,120.8,118.8,111.6,109.7,32.8,19.0.HR-MS(ESI)m / z calcd for C 16 H 16 NOSe + [M+H] + :318.0397,found:318.0402.

[0134] Example 37: Preparation of Product 39

[0135] Replacing benzeneselenic acid with 4-ethylbenzeneselenic acid in Example 1 yielded a white solid 39, with a yield of 51%.

[0136] 3-((4-ethylphenyl)seleninyl)-1-methyl-1H-indole(39) 1 H NMR(600MHz, CDCl3)δ7.58(d,J=8.7Hz,2H),7.40(d,J=8.1Hz,1H),7.23(s,1H),7.18–7.10(m,3H), 7.08(d,J=8.3Hz,1H),6.97–6.92(m,1H),3.54(s,3H),2.52(q,J=7.6Hz,2H),1.08(t,J=8.3Hz,3H). 13 C NMR (150MHz, CDCl3) δ147.1,138.0,137.3,131.8,128.6,126.4,125.7,122.7,120.8,119.3,112.8,109.8,32.9,28.3,15.0.HR-MS(ESI)m / z calcd forC 17 H 18 NOSe,[M+H] + :332.0554,found:332.0557.

[0137] Example 38: Preparation of Product 40

[0138] Replacing benzeneselenic acid with 4-methoxybenzene selenite in Example 1 yielded a white solid 40 in 65% yield.

[0139] 3-((4-methoxyphenyl)seleninyl)-1-methyl-1H-indole(40) 1 H NMR(600MHz, CDCl3)δ7.52–7.48(m,2H),7.32(d,J=7.7Hz,1H),7.17(s,1H),7.12 –6.94(m,2H),6.87(d,J=7.2Hz,1H),6.76–6.73(m,2H),3.51(s,3H),3.42(s,3H). 13 CNMR(150MHz, CDCl3)δ161.1,137.0,131.5,127.6,126.9,125.3,122.4,120.4,118.9,114.3,112.4,109.6,54.7,32.5.HR-MS(ESI)m / z calcd for C 16 H 16 NO2Se, [M+H] + :334.0346,found:334.0349.

[0140] Example 39: Preparation of Product 41

[0141] Replacing benzeneselenic acid with 3,4,5-trimethoxybenzeneselenic acid in Example 1 yielded white solid 41 with a yield of 76%.

[0142] 1-methyl-3-((3,4,5-trimethoxyphenyl)seleninyl)-1H-indole(41) 1 H NMR (600MHz, CDCl3) δ7.54(d,J=7.0Hz,1H),7.32(s,1H),7.29(d,J=8.3Hz,1H),7.23(t, J=7.4Hz,1H),7.10(t,J=8.1Hz,1H),7.02(s,2H),3.82(s,3H),3.81(s,6H),3.73(s,3H). 13 CNMR(150MHz, CDCl3)δ153.6,140.0,137.6,135.2,132.1,126.0,123.2,121.4,119.4,113.1,110.2,103.5,60.9,56.4,33.3.HR-MS(ESI)m / z calcd for C 18 H 20 NO4Se,[M+H] + :394.0558,found:394.0562.

[0143] Example 40: Preparation of Product 42

[0144] Replacing benzeneselenic acid with 4-fluorobenzene selenite in Example 1 yielded a white solid 42 with a yield of 53%.

[0145] 3-((4-fluorophenyl)seleninyl)-1-methyl-1H-indole(42) 1 H NMR (400MHz, CDCl3) δ7.82–7.75(m,2H),7.43(m,2H),7.34(d,J=8.3Hz,1H), 7.26(t,J=7.6Hz,1H),7.21–7.14(m,2H),7.10(t,J=7.6Hz,1H),3.80(s,3H). 13C NMR (100MHz, CDCl3) δ164.3 (d, J = 251.2Hz), 137.6, 136.3, 132.1, 128.9 (d, J = 8.7Hz), 125.8, 123.3, 121.4, 119.4, 116.7 (d, J = 22.2Hz), 110.2, 33.4. 19 F NMR(375MHz,CDCl3)δ-108.5.HR-MS(ESI)m / z calcd forC 15 H 13 NOSeF,[M+H] + :322.0146,found:322.0152.

[0146] Example 41: Preparation of Product 43

[0147] Replacing benzeneselenic acid with 4-chlorobenzeneselenic acid in Example 1 yielded a white solid 43 with a yield of 63%.

[0148] 3-((4-chlorophenyl)seleninyl)-1-methyl-1H-indole(43) 1 H NMR (400MHz, CDCl3) δ7.68(d,J=10.5Hz,2H),7.44–7.34(m,4H),7.28(d,J=8.3Hz,1H),7.21(t,J=8.2Hz,1H),7.06(t,J=8.1Hz,1H),3.73(s,3H). 13 C NMR(100MHz, CDCl3)δ139.5,137.6,137.2,132.2,129.6,128.1,125.7,123.3,121.5,119.4,110.2,33.46.HR-MS(ESI)m / zcalcd for C 15 H 13 NOClSe,[M+H] + :337.9851,found:337.9857.

[0149] Example 42: Preparation of Product 44

[0150] Replacing benzeneselenic acid with 4-bromobenzene selenite in Example 1 yielded a white solid 44 in 88% yield.

[0151] 3-((4-bromophenyl)seleninyl)-1-methyl-1H-indole(44) 1H NMR (400MHz, CDCl3) δ7.62(d,J=8.1Hz,2H),7.54(d,J=8.0Hz,2H),7.42(d,J=8.1Hz,1H),7. 35(s,1H),7.28(d,J=8.3Hz,1H),7.21(t,J=7.7Hz,1H),7.06(t,J=7.4Hz,1H),3.73(s,3H). 13 CNMR(100MHz, CDCl3)δ140.2,137.6,132.5,132.2,128.3,125.7,125.5,123.3,121.5,119.4,110.2,33.4.HR-MS(ESI)m / z calcd for C 15 H 13 NOSeBr,[M+H] + :381.9346,found:381.9351.

[0152] Example 43: Preparation of Product 45

[0153] Replacing benzeneselenic acid with 2-bromobenzeneselenic acid in Example 1 yielded a white solid 45, with a yield of 57%.

[0154] 3-((2-bromophenyl)seleninyl)-1-methyl-1H-indole(45) 1 H NMR(400MHz, CDCl3)δ8.28(d,J=7.9Hz,1H),7.68(d,J=8.0Hz,1H),7.61–7.52(m, 1H),7.44(d,J=8.0Hz,1H),7.35–7.16(m,4H),7.11(t,J=7.5Hz,1H),3.70(s,3H). 13 CNMR(100MHz,cdcl3)δ141.5,137.1,132.8,132.5,132.0,128.3,128.1,126.3,123.0,122.4,121.3,119.6,112.2,110.1,33.4.HR-MS(ESI)m / z calcd for C 15 H 13 NOSeBr,[M+H] + :381.9346,found:381.9351.

[0155] Example 44: Preparation of Product 46

[0156] Replacing benzeneselenic acid with 4-chlorobenzeneselenic acid in Example 1 yielded a white solid 46 with a yield of 75%.

[0157] 5-chloro-1,2-dimethyl-3-((3,4,5-trimethoxyphenyl)seleninyl)-1H-indole(46) 1 HNMR (600MHz, CDCl3) δ7.24(m,1H),6.93(d,J=8.7Hz,1H),6.85(m,3H),3.68(s,3H),3.66(s,6H),3.41(s,3H),2.41(s,3H). 13 C NMR (150MHz, CDCl3) δ153.7,142.3,139.7,135.3,134.8,126.3,126.2,122.0,118.1,110.3,109.0,103.2,60.5,56.1,29.6,11.3.HR-MS(ESI)m / z calcd for C 19 H 21 NO4ClSe,[M+H] + :442.0324,found:442.0328.

[0158] Example 45: Preparation of Product 47

[0159] Replacing benzeneselenic acid with 2-naphthylselenic acid in Example 1 yielded a white solid 47, with a yield of 88%.

[0160] 1-methyl-3-(naphthalen-2-ylseleninyl)-1H-indole(47) 1 H NMR (400MHz, CDCl3) δ8.50 (s, 1H), 7.97–7.91 (m, 1H), 7.91–7.82 (m, 2H), 7.65 (d, J = 6.9Hz, 1H), 7.59–7. 49(m,3H),7.37(s,1H),7.30(d,J=8.3Hz,1H),7.23(t,J=7.8Hz,1H),7.06(t,J=7.6Hz,1H),3.74(s,3H). 13 C NMR (151MHz, CDCl3) δ137.7,134.5,133.2,132.3,129.5,128.6,128.1,127.7,127.2,127.0,126.2,123.3,122.8,121.51,119.6,110.2,33.4.

[0161] Example 46: Preparation of Product 48

[0162] (S)-2-(4-isobutylphenyl)propionic acid-1-methyl-5-indole methyl ester, in place of 1-methylindole in Example 1, yielded a white solid 48 in 67% yield.

[0163] (1-methyl-3-(phenylseleninyl)-1H-indol-5-yl)methyl(2S)-2-(4-isobutylphenyl)pr opanoate(48) 1 H NMR (400MHz, CDCl3) δ7.82–7.75(m,2H),7.49–7.44(m,3H),7.43–7.36(m,2H),7.20–7.14(m,3H),7.08–7.02(m,2H),6.98(d,J=8.5Hz,1 H),5.17(s,2H),3.76–3.62(m,4H),2.42(d,J=7.1Hz,2H),1.82(hept,J=13.6,6.8Hz,1H),1.47(d,J=7.2Hz,3H),0.88(d,J=6.7Hz,6H). 13 C NMR (100MHz, CDCl3) δ174.4,140.5,137.6,137.5,132.6,131.3,130.9,129.4,129.3,127.23,126.6,12 5.7,121.5,121.4,119.5,109.8,109.7,66.6,45.1,44.9,33.3,30.1,22.3,18.5,18.4.HR-MS(ESI)m / z calcdfor C 19 H 21 NO4ClSe,[M+H] + :442.0324,found:442.0328.

[0164] Example 47: Preparation of Product 49

[0165] Replacing 1-methylindole in Example 1 with 1-methyl-2-phenyl-5-methoxyindole yielded a white solid 49, with a yield of 87%.

[0166] 5-methoxy-1-methyl-2-phenyl-3-(phenylseleninyl)-1H-indole(48) 1H NMR (600MHz, CDCl3) δ7.79–7.74(m,2H),7.54–7.52(m,5H),7.47–7.37(m,3H),7.20(d,J=8 .9Hz,1H),6.84(dd,J=8.9,2.5Hz,1H),6.72(d,J=2.5Hz,1H),3.60(s,3H),3.53(s,3H).13C NMR (150MHz, CDCl3) δ155.2,145.6,140.7,132.9,130.9,130.4,129.8,129.2 ,128.9,126.9,126.0,114.0,111.1,110.9,101.2,55.5,31.2.HR-MS(ESI)m / z calcd forC 22 H 19 NO2Se, [M+H] + :409.0581,found:409.0588.

[0167] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0168] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention. Therefore, the protection scope of this invention patent should be determined by the appended claims.

Claims

1. A method for the convenient synthesis of diarylselenide sulfoxide under mild conditions without the need for a catalyst, characterized in that, The reaction proceeds according to the following reaction equation: The process includes the following steps: using aromatic hydrocarbon compounds represented by Formula I and selenite compounds represented by Formula II as raw materials, a reaction is carried out, and after the reaction is completed, the diaryl selenite sulfoxide compounds represented by Formula III are obtained by separation and purification. Ar in the aromatic hydrocarbon compound represented by Formula I 1 For substituted or unsubstituted C 6-20 Aromatics, substituted or unsubstituted C 4-20 One of the heteroaromatic hydrocarbons; Ar in the selenite compound represented by Formula II 2 For substituted or unsubstituted C 6-20 aryl, substituted or unsubstituted C 3-20 One of the heteroaryl groups.

2. The method according to claim 1, characterized in that, The Ar 1 It is one of the following: substituted or unsubstituted indole, benzene, or thiophene; the Ar 2 Aryl groups, whether substituted or unsubstituted.

3. The method according to claim 2, characterized in that, The Ar 1 The Ar is an indole substituted with one or more of alkyl, alkynyl, aryl, heteroaryl, alkylaryl, alkenyl, halogen, heteroalkyl, nitro, cyano, fluoroalkyl, carboxyl, ester, acyloxy, or acyl groups; a benzene substituted with one or more heteroalkyl groups; or a thiophene substituted with one or more heteroalkyl groups. 2 It is an aryl group that is substituted by one or more of alkyl, alkoxy, or halogen groups.

4. The method according to claim 3, characterized in that, The Ar 1 The following are listed: 1-methylindole, 1,4-dimethylindole, 1-methyl-4-fluoroindole, 1-methyl-4-bromoindole, 1,5-dimethylindole, 1-methyl-5-methoxyindole, 1-methyl-5-fluoroindole, 1-methyl-5-chloroindole, 1-methyl-5-bromoindole, 1-methyl-5-iodoindole, 1-methyl-5-nitroindole, 1,2-dimethylindole, 1,2-dimethyl-5-methoxyindole, 1-methyl-6-fluoroindole, 1-methylindole-6-carboxaldehyde, methyl indole-6-carboxylate, 1-methyl-6-cyanoindole, 1-methyl-6-nitroindole, 1-methyl-6-trifluoromethylindole. One of the following: 1,7-dimethylindole, 1-methyl-7-methoxyindole, 1-isopropylindole, 1-allylindole, 1-benzylindole, 1-(2-pentynyl)indole, 1-phenylindole, 2-methyl-1-ethylindole, 1-ethyl-2-phenylindole, 1-benzylindole-6-carboxylic acid, 1-methyl-2-phenyl-5-methoxyindole, 1,2-dimethyl-5-chloroindole, (S)-2-(4-isobutylphenyl)propionate-1-methyl-5-indole methyl ester, 1,3,5-trimethoxybenzene, N-methylaniline, 2-methoxythiophene, 3-methoxythiophene, and 3,4-ethylenedioxythiophene; The Ar 2 It is one of 2-methylphenyl, 4-methylphenyl, 4-ethylphenyl, 4-methoxyphenyl, 3,4,5-trimethoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 2-bromophenyl, 3,4,5-trimethoxyphenyl, and 2-naphthyl.

5. The method according to claim 1, characterized in that, The reaction is carried out in a solvent, which is any one or a mixture of several of the following: water, N,N-dimethylformamide, dimethyl sulfoxide, ethanol, 2,2,2-trifluoroethanol, 1,1,1,3,3,3-hexafluoro-2-propanol, methanol, isopropanol, tert-butanol, polyethylene glycol, ether solvents, and halogenated hydrocarbons, preferably one or a mixture of several of the following: ethanol, 2,2,2-trifluoroethanol, 1,1,1,3,3,3-hexafluoro-2-propanol, methanol, and isopropanol.

6. The method according to any one of claims 1-5, characterized in that, The molar ratio of the aromatic compound represented by Formula I to the selenite compound represented by Formula II is 1-10:1-10.

7. The method according to any one of claims 1-5, characterized in that, The reaction temperature is -10 to 120°C, and the reaction time is 2 to 48 hours.

8. The method according to any one of claims 1-5, characterized in that, The method is carried out in an inert atmosphere, an oxygen atmosphere, or an air atmosphere.

9. The method according to any one of claims 1-5, characterized in that, The separation and purification process includes the following steps: after the reaction is completed, the reaction solvent and reactants are directly concentrated to obtain the residue, which is then separated by silica gel column chromatography to obtain the diaryl selenide sulfoxide compound represented by Formula III.

10. The method according to any one of claims 1-5, characterized in that, The separation and purification process includes the following steps: after the reaction is completed, the reaction solvent and reactants are directly concentrated to obtain a residue, which is then recrystallized to obtain the diaryl selenide sulfoxide compound represented by Formula III.

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